Impotence and infertility are presently untreatable complications in over 50% of diabetic males. Initially thought to be due entirely to autonomic dysfunction, recent evidence in diabetic animal models and man suggest that these diabetic complications may in fact be due to alterations of the pituitary-testicular axis which in turn are correctable with appropriate therapy. Our proposed project would include an in depth evaluation of the pituitary-testicular axis in diabetic rat and man and the role of insulin in the modulation of this axis. The diabetic rat models to be studied would include both the male streptozotocin diabetic wistar rat as well as the male spontaneously diabetic Bio-Breeding (BB) rats. Studies in rats would include specific radioimmunoassays of serum testosterone prolactin and androgen-binding protein (ABP) as well as urinary FSH and LH. Using an isolated testes perfusion model partly developed by this investigator, testosterone response to HCG will be evaluated in both diabetic animal models using animals treated and untreated with insulin. The isolated testes perfusion technique will also be utilized as a method of fixation for qualitative and quantitative morphometric evaluation of the testes utilizing both light and electromicroscopy. Again using the technique of isolated testes profusion, protein synthesis will be measured in both animal models treated and untreated with insulin. Evaluation of the pituitary-testicular-axis in diabetic man would include specific radioimmunoassays of serum total and free testosterone, glucose, prolactin, and urinary FSH and LH during the fasting state and glucose, free and total testosterone during moderate exercise on a bicycle ergometer. The rationale for studies during exercise will be described. A thorough clinical evaluation using nocturnal penile tumesence studies will be performed on all participants to explore the relationship of male infertility and impotence to alterations in the pituitary-testicular axis. A limited number of testicular biopsies will also be performed in infertile oligospermic diabetic males for quantitative morphometric evaluation at the level of light and electron microscopy. Reversibility of pituitary-testicular changes will be investigated.